PMID- 28666426
OWN - NLM
STAT- MEDLINE
DCOM- 20180402
LR  - 20181113
IS  - 1746-6148 (Electronic)
IS  - 1746-6148 (Linking)
VI  - 13
IP  - 1
DP  - 2017 Jul 1
TI  - Prediction of marbofloxacin dosage for the pig pneumonia pathogens Actinobacillus 
      pleuropneumoniae and Pasteurella multocida by pharmacokinetic/pharmacodynamic 
      modelling.
PG  - 209
LID - 10.1186/s12917-017-1128-y [doi]
LID - 209
AB  - BACKGROUND: Bacterial pneumonia in pigs occurs widely and requires antimicrobial 
      therapy. It is commonly caused by the pathogens Actinobacillus pleuropneumoniae 
      and Pasteurella multocida. Marbofloxacin is an antimicrobial drug of the 
      fluoroquinolone class, licensed for use against these organisms in the pig. In 
      recent years there have been major developments in dosage schedule design, based 
      on integration and modelling of pharmacokinetic (PK) and pharmacodynamic (PD) 
      data, with the objective of optimising efficacy and minimising the emergence of 
      resistance. From in vitro time-kill curves in pig serum, PK/PD breakpoint Area 
      under the curve (AUC) (24h) /minimum inhibitory concentration (MIC) values were 
      determined and used in conjunction with published PK, serum protein binding data 
      and MIC distributions to predict dosages based on Monte Carlo simulation (MCS). 
      RESULTS: For three levels of inhibition of growth, bacteriostasis and 3 and 
      4log(10) reductions in bacterial count, mean AUC(24h)/MIC values were 20.9, 45.2 
      and 71.7 h, respectively, for P. multocida and 32.4, 48.7 and 55.5 h for A. 
      pleuropneumoniae. Based on these breakpoint values, doses for each pathogen were 
      predicted for several clinical scenarios: (1) bacteriostatic and bactericidal 
      levels of kill; (2) 50 and 90% target attainment rates (TAR); and (3) single 
      dosing and daily dosing at steady state. MCS for 90% TAR predicted single doses 
      to achieve bacteriostatic and bactericidal actions over 48 h of 0.44 and 
      0.95 mg/kg (P. multocida) and 0.28 and 0.66 mg/kg (A. pleuropneumoniae). For 
      daily doses at steady state, and 90% TAR bacteriostatic and bactericidal actions, 
      dosages of 0.28 and 0.59 mg/kg (P. multocida) and 0.22 and 0.39 mg/kg (A. 
      pleuropneumoniae) were required for pigs aged 12 weeks. Doses were also predicted 
      for pigs aged 16 and 27 weeks. CONCLUSIONS: PK/PD modelling with MCS approaches 
      to dose determination demonstrates the possibility of tailoring clinical dose 
      rates to a range of bacterial kill end-points.
FAU - Dorey, Lucy
AU  - Dorey L
AUID- ORCID: 0000-0003-3596-7919
AD  - Comparative Biological Sciences, Royal Veterinary College, London University, 
      London, UK. ldorey@rvc.ac.uk.
FAU - Pelligand, Ludovic
AU  - Pelligand L
AD  - Comparative Biological Sciences, Royal Veterinary College, London University, 
      London, UK.
FAU - Lees, Peter
AU  - Lees P
AD  - Comparative Biological Sciences, Royal Veterinary College, London University, 
      London, UK.
LA  - eng
PT  - Journal Article
DEP - 20170701
PL  - England
TA  - BMC Vet Res
JT  - BMC veterinary research
JID - 101249759
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Fluoroquinolones)
RN  - 8X09WU898T (marbofloxacin)
SB  - IM
MH  - Actinobacillus pleuropneumoniae/*drug effects
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fluoroquinolones/*pharmacokinetics/pharmacology
MH  - Microbial Sensitivity Tests/veterinary
MH  - Models, Biological
MH  - Monte Carlo Method
MH  - Pasteurella multocida/*drug effects
MH  - Pneumonia, Bacterial/drug therapy/metabolism/*veterinary
MH  - Swine
PMC - PMC5493866
OTO - NOTNLM
OT  - A. Pleuropneumoniae
OT  - Marbofloxacin
OT  - Monte Carlo simulation
OT  - P. Multocida
OT  - Pharmacokinetic/Pharmacodynamic
OT  - Pig
OT  - Time-kill curves
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2017/07/02 06:00
MHDA- 2018/04/03 06:00
PMCR- 2017/07/01
CRDT- 2017/07/02 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/06/22 00:00 [accepted]
PHST- 2017/07/02 06:00 [entrez]
PHST- 2017/07/02 06:00 [pubmed]
PHST- 2018/04/03 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - 10.1186/s12917-017-1128-y [pii]
AID - 1128 [pii]
AID - 10.1186/s12917-017-1128-y [doi]
PST - epublish
SO  - BMC Vet Res. 2017 Jul 1;13(1):209. doi: 10.1186/s12917-017-1128-y.